Pharmacotherapy of Insomnia
First-Line Pharmacotherapy Recommendation
Start with short-intermediate acting benzodiazepine receptor agonists (BzRAs) or ramelteon as first-line pharmacotherapy for chronic insomnia, selecting the specific agent based on whether the primary complaint is sleep onset versus sleep maintenance difficulty. 1
Treatment Selection Algorithm
For Sleep Onset Insomnia
- Zaleplon 10 mg - ultra-short acting, ideal for difficulty falling asleep 1, 2
- Zolpidem 10 mg (5 mg in elderly) - effective for both onset and maintenance 1, 2
- Ramelteon 8 mg - melatonin receptor agonist, FDA-approved specifically for sleep onset difficulty with proven efficacy up to 6 months 1, 3
- Triazolam 0.25 mg - not first-line due to rebound anxiety risk 1
For Sleep Maintenance Insomnia
- Eszopiclone 2-3 mg - proven efficacy for both onset and maintenance, the only non-benzodiazepine evaluated long-term (up to 12 months) without tolerance or rebound 1, 4
- Zolpidem 10 mg (5 mg in elderly) - dual action for onset and maintenance 1, 2
- Temazepam 15 mg (7.5 mg in elderly/debilitated) - intermediate-acting benzodiazepine for both onset and maintenance 1, 2
Second-Line Pharmacotherapy Options
When first-line BzRAs fail or are contraindicated:
- Doxepin 3-6 mg - specifically for sleep maintenance through H1 receptor antagonism 1, 2, 5
- Suvorexant - orexin receptor antagonist reducing wake after sleep onset by 16-28 minutes 1, 5
- Sedating antidepressants - consider when comorbid depression/anxiety present 1
Agents NOT Recommended
Avoid these commonly used but ineffective or unsafe options:
- Trazodone - explicitly not recommended by AASM despite widespread off-label use 1, 2, 5
- Over-the-counter antihistamines (diphenhydramine) - lack efficacy data and cause daytime sedation, delirium risk in elderly 1, 2, 5
- Melatonin, valerian, L-tryptophan - insufficient evidence 2
- Tiagabine - not recommended, seizure risk 5
- Antipsychotics (quetiapine, olanzapine) - insufficient evidence, significant metabolic/neurological risks 5
- Barbiturates and chloral hydrate - outdated, dangerous 1, 2
Critical Implementation Principles
Dosing Strategy
- Use lowest effective dose for shortest duration 1
- Elderly patients require dose reduction (e.g., zolpidem 5 mg maximum) due to fall and cognitive impairment risk 1
- Consider "as-needed" dosing (up to 5 nights/week) rather than nightly use to prevent tolerance 6
Mandatory Behavioral Therapy Integration
Pharmacotherapy must be supplemented with Cognitive Behavioral Therapy for Insomnia (CBT-I), not used as monotherapy. 1, 2, 5 CBT-I has superior long-term efficacy compared to medications alone and prevents relapse after medication discontinuation.
Monitoring Requirements
- Follow patients every few weeks initially to assess effectiveness and side effects 1, 2
- If insomnia persists beyond 7-10 days, reevaluate for comorbid sleep disorders (sleep apnea, restless legs syndrome) 5
- Taper medications when conditions allow to prevent discontinuation symptoms 1
Common Pitfalls to Avoid
- Using sedating agents without matching to sleep onset versus maintenance pattern - zaleplon won't help maintenance insomnia, doxepin won't help onset 1
- Prescribing trazodone - despite common practice, AASM explicitly recommends against it 1, 2, 5
- Using OTC antihistamines - no efficacy data, problematic side effects especially in elderly 1, 2
- Continuing long-term without reassessment - periodic evaluation mandatory 1, 2
- Failing to screen for drug interactions and contraindications before prescribing 1
- Combining multiple sedatives - significantly increases fall, fracture, and cognitive impairment risk 1
Special Populations
Elderly Patients
- Require 50% dose reduction (zolpidem 5 mg, temazepam 7.5 mg) 1, 2
- Higher risk of falls, cognitive impairment, complex sleep behaviors 1
- Avoid long-acting benzodiazepines entirely 1